3'-C-Substituted ribonucleoside derivatives represented by the following formula (6): ##STR2## (wherein B represents a nucleic acid base which may have a substituent and Z represents an ethynyl group which may be substituted by a trialkylsilyl group) exhibit excellent antitumor activities, and thus these compounds are useful as antitumor agents (International Patent Application No. PCT/JP95/02554).
Conventionally, 3'-C-substituted ribonucleoside derivatives have been synthesized through nucleophilic addition to 3'-ketonucleoside (Chem. Pharm. Bull., 35, 2605 (1987), Tetrahedron, 47, 1727 (1991)). However, when 3'-ketonucleoside having a protected hydroxyl group at the 5'-position is subjected to nucleophilic addition, nucleosides of the xylose type are mainly formed, and the target ribose type nucleosides can hardly be obtained. Also, Tetrahedron Letters, 36, 10331-1034 (1995) describes that the compound of interest, i.e., 3'-C-substituted ribonucleoside, can be synthesized through nucleophilic addition to 3'-KETONUCLEOSIDE having unprotected hydroxy at the 5'-position. However, since 5'-O-unsubstituted-3'-ketonucleoside is a very unstable compound, it is not suitable for use as an industrial synthesis intermediate.
Independently, it has been reported that the compound of interest, i.e., a 3'-C-substituted ribonucleoside derivative, can be synthesized through reaction between a 3-C-substituted ribofuranose derivative and a silylated nucleic acid base in an aprotic solvent in the presence of a Lewis acid (International Patent Application No. PCT/JP95/02554). However, this process is not suitable for industrial synthesis of the compound, for it requires a purification procedure by column chromatography because respective intermediates cannot be obtained as crystals. According to this invention, the hydroxyl group at the 3-position of xylofuranose is oxidized to obtain an intermediate 3-ketofuranose, wherein the oxidation step generally includes use of dimethylsulfoxide or chromic acid. In the case of dimethylsulfoxide, dimethylsulfide having foul is generated. Chromic acid is harmful heavy metal that may have adverse effects on the environment. Therefore, neither case is preferred.
Accordingly, the object of the present invention is to provide a stable intermediate for preparing 3'-C-substituted ribonucleoside derivatives industrially and economically, with simplicity and efficiency, without use of a harmful reagent, as well as to provide a process for preparing the intermediate.